Note that this study found that across the registries, the therapy receiving excess high-risk patients had worse mortality. Accounting for differential allocation of higher-risk patients, primary angioplasty gave lower mortality.

In a meta-analysis, the therapy receiving excess high-risk patients had worse mortality across several registry studies, and accounting for this difference in higher-risk patients gave angioplasty a 22% lower mortality (P=0.029), Sayan Sen, MRCP, of the National Heart and Lung Institute in London, and colleagues, reported online in Circulation: Cardiovascular Quality and Outcomes.

Randomized, controlled trials have consistently shown a benefit for primary angioplasty in STEMI over fibrinolysis. But real-world observational experience -- largely via registry studies -- have found that both treatments have equivalent survival.

Allocation bias is a recognized limitation of registries, as randomized trials may selectively include patients who garner more benefit from PCI.

In registries, on the other hand, clinicians can allocate therapy based on their assessment of a patient's needs. Some may feel higher risk patients should be treated with PCI, while others may judge fibrinolysis is safer.

So Sen and colleagues constructed a model to demonstrate the potential effects of allocation bias, looking at published registries totaling 55,022 patients.

As expected, they found that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy involving excess high-risk patients had worse mortality.

In six of the eight registries, more high-risk patients were allocated to PCI, they reported.

They found that the unequal distribution of high-risk status accounted for most of the variance between registries, and accounting for this differential allocation of higher-risk patients gave primary angioplasty a 22% lower mortality (OR 0.78, 95% CI 0.64 to 0.97, P=0.029).

The researchers also derived a formula called the "number needed to abolish," in order to highlight situations in which comparative effectiveness studies are particularly vulnerable to this kind of bias.

Essentially, only a 5.4% excess prevalence of high-risk patients in the PCI arm was sufficient to mask the mortality benefit of PCI, they found (P=0.015).

"Because a disproportionate number of deaths in STEMI occur in higher-risk patients and the absolute difference in mortality between therapies is often small, only minor preferential allocation of higher-risk patients to one therapy can easily have a surprisingly large effect on relative mortality between therapies," they wrote.

The study was limited because it is unclear how the number of studies, the weight of each study, the extent of heterogeneity, and the potential for aggregation bias all influence the probability of producing false positive or false negative results, the researchers wrote.

Still, they concluded that their findings support the notion that "preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials."

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